Atherosclerosis, closely resembling that in man, was induced in specific pathogen free chickens by Marek's disease virus. These findings may have an important bearing on our understanding of the etiology and pathogenesis of human arteriosclerosis since there is persistent and widespread infection of human populations with up to five different herpesviruses. The objectives of this proposal are: A. To establish more precisely the role of Marek's disease herpesvirus in the pathogenesis of atherosclerosis by (1) Investigating the relationships between genetic resistance of the host and virus virulence in determining the expression of atherosclerotic lesions (2) Identifying viral genome in the cells of atherosclerotic lesions by in situ hybridization and correlating the extent of viral transformation with development of atherosclerosis (3) Elucidating the mechanisms responsible for lipid accumulation in vivo in virus-infected arterial cells (4) Examining connective tissue components in the arterial wall to determine a possible role of these proteins in the process of arterial lipid accumulation in virus-induced atherosclerosis (5) Characterizing endothelial changes in early arterial lesions induced by MDV, and (6) Studying the role of cell-mediated immunity in the pathogenesis of the atherosclerotic lesion. B. In addition, we intend to investigate a possible role of human herpesvirus in the development of atherosclerosis by studying the effect of human herpesviruses on the metabolism of cultured human vascular smooth muscle cells.